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Effects of the combined continuous administration of morphine and the high‐efficacy 5‐HT 1A agonist, F 13640 in a rat model of trigeminal neuropathic pain
Author(s) -
Deseure Kristof R.,
Adriaensen Hugo F.,
Colpaert Francis C.
Publication year - 2004
Publication title -
european journal of pain
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.305
H-Index - 109
eISSN - 1532-2149
pISSN - 1090-3801
DOI - 10.1016/j.ejpain.2004.01.002
Subject(s) - agonist , medicine , anesthesia , neuropathic pain , morphine , administration (probate law) , pharmacology , receptor , political science , law
F 13640 is a recently discovered high‐efficacy 5‐HT 1A receptor agonist that has demonstrated robust anti‐allodynic efficacy in a rat model of trigeminal neuropathic pain upon acute and continuous administration. In this model, continuous morphine infusion (5 mg/day) was shown to be effective during the first week of its administration but became almost completely ineffective by the end of the second week; F 13640's effectiveness (0.63 mg/day) remained unchanged during two weeks. Here, we examined the effects of combining F 13640 infusion with that of morphine. During the first week, the combination of the two agents produced a magnitude of effect that was similar to that of morphine when given alone and larger than that of F 13640 alone. During the second week, the combination produced an effect that was similar to that of F 13640 alone, and more effective than that of morphine alone. The latter data suggest that the 5‐HT 1A agonist, F 13640, inhibits the development of tolerance to morphine in this model. However, it is also possible that little, if any, interaction occurred between the different mechanisms initiated by opioid and 5‐HT 1A receptor activation, and that the anti‐allodynic effect that remained by the end of the two‐week treatment period is due solely to 5‐HT 1A receptor activation. The stable effects of F 13640 during the second week of treatment surpassed those of morphine and were not improved by the addition of morphine to F 13640.